Who can enter
- Children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) with mutations in the IL-7R/JAK-STAT signaling pathway, who have had an inadequate response to previous treatment (refractory) or whose disease has come back (relapse)
- Age: 1 to 21 years
Goal
The goal of this study is to investigate whether the combination of the drugs ruxolitinib and venetoclax is tolerable, safe and effective in combination with dexamethasone, cyclophosphamide and cytarabine. This is tested in patients who have had an inadequate response to previous treatments (refractory) or whose disease has come back (relapse).
Background
Certain changes (mutations) present in leukemia or lymphoma cells are responsible for increased and uncontrolled cell growth. Known changes that act like this are mutations in several genes that are part of the IL7R/JAK-STAT signaling pathway. Certain proteins control the growth of many cancers. Amongst those are the so-called tyrosine kinases (such as JAK and STAT kinase).
The drug ruxolitinib inhibits the action of these enzymes, thereby inhibiting cell divisions and thus the growth of leukemia or lymphoma cells. Venetoclax targets a particular protein that is increased in leukemia or lymphoma cells and prevents the cancerous cells from dying naturally (this protein is called: BCL2 protein). Venetoclax inhibits this BCL2 protein, enabling the leukemia cells to die.
Dexamethasone, cyclophosphamide and cytarabine are drugs that can cause leukemia and lymphoma cells to die using other mechanisms of action.